A review on vitamin A deficiency and depleted immunity in South Asia: From deficiency to resilience.

In the developing world, the twin challenges of depleted health and growing issue of food waste management loom large, demanding simultaneous attention and innovative solutions. This review explores how these issues can be effectively mitigated while shedding light on the transformative impact of food waste valorization on health management. A spotlight is cast on vitamin A deficiency (VAD), an acute public health concern, especially prevalent in South Asia, driven by economic constraints, sociocultural factors, inadequate diets, and poor nutrient absorption. VAD's devastating effects are exacerbated by limited education, lack of sanitation, ineffective food regulations, and fragile monitoring systems, disproportionately affecting children and women of childbearing age. Recent studies in South Asian countries have revealed rising rates of illness and death, notably among children and women of childbearing age, due to VAD. To address inadequate dietary intake in children utilizing vegetable waste, particularly from carrots and beetroot, which are rich in ß-carotene, and betalains, respectively, offers a sustainable solution. Extracting these compounds from vegetable waste for supplementation, fortification, and dietary diversification could significantly improve public health, addressing both food waste and health disparities economically. This approach presents a compelling avenue for exploration and implementation. In summary, this review presents an integrated approach to tackle health and food waste challenges in the developing world. By tapping into the nutritional treasure troves within vegetable waste, we can enhance health outcomes while addressing food waste, forging a brighter and healthier future for communities in need.

Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health.

Twin studies suggest a considerable genetic contribution to the variability in 25-hydroxyvitamin D (25(OH)D) concentrations, reporting heritability estimates up to 80% in some studies. While genome-wide association studies (GWAS) suggest notably lower rates (13−16%), they have identified many independent variants that associate with serum 25(OH)D concentrations. These discoveries have provided some novel insight into the metabolic pathway, and in this review we outline findings from GWAS studies to date with a particular focus on 35 variants which have provided replicating evidence for an association with 25(OH)D across independent large-scale analyses. Some of the 25(OH)D associating variants are linked directly to the vitamin D metabolic pathway, while others may reflect differences in storage capacity, lipid metabolism, and pathways reflecting skin properties. By constructing a genetic score including these 25(OH)D associated variants we show that genetic differences in 25(OH)D concentrations persist across the seasons, and the odds of having low concentrations (<50 nmol/L) are about halved for individuals in the highest 20% of vitamin D genetic score compared to the lowest quintile, an impact which may have notable influences on retaining adequate levels. We also discuss recent studies on personalized approaches to vitamin D supplementation and show how Mendelian randomization studies can help inform public health strategies to reduce adverse health impacts of vitamin D deficiency.

Interactions between Vitamin D Genetic Risk and Dietary Factors on Metabolic Disease-Related Outcomes in Ghanaian Adults.

The Ghanaian population is experiencing an upsurge in obesity and type 2 diabetes (T2D) due to rapid urbanization. Besides dietary factors, vitamin D-related genetic determinants have also been shown to contribute to the development of obesity and T2D. Hence, we aimed to examine the interactions between dietary factors and vitamin D-related genetic variants on obesity and T2D related outcomes in a Ghanaian population. Three hundred and two healthy Ghanaian adults (25-60 years old) from Oforikrom, Municipality in Kumasi, Ghana were randomly recruited and had genetic tests, dietary consumption analysis, and anthropometric and biochemical measurements of glucose, HbA1c, insulin, cholesterol, and triglycerides taken. A significant interaction was identified between vitamin D-GRS and fiber intake (g/day) on BMI (pinteraction = 0.020) where those who were consuming low fiber (≤16.19 g/d) and carrying more than two risk alleles for vitamin D deficiency (p = 0.01) had a significantly higher BMI. In addition, an interaction between vitamin D-GRS and fat intake (g/day) on HbA1c (total fat, pinteraction = 0.029) was found, where participants who had a lower total fat intake (≤36.5 g/d), despite carrying more than two risk alleles, had significantly lower HbA1c (p = 0.049). In summary, our study has identified novel gene-diet interactions of vitamin D-GRS with dietary fiber and fat intakes on metabolic traits in Ghanaian adults.

Association between pre-pregnancy body mass index and gestational weight gain on pregnancy outcomes: a cohort study in Indonesian pregnant women.

BACKGROUND: Pre-pregnancy BMI (PP BMI) and gestational weight gain (GWG) are prominent anthropometric indicators for maternal nutritional status and are related to an increased risk of adverse pregnancy outcomes. This study aimed to determine the factors affecting total GWG, PP BMI and pregnancy outcomes among pregnant women in West Sumatra, Indonesia. METHODS: This observational analysis was conducted among healthy women in the Vitamin D Pregnant Mother (VDPM) cohort study. A total of 195 pregnant women and their newborn babies were enrolled, and information regarding their socio-demographic characteristics, obstetric history, dietary intake and anthropometric data were assessed through direct interviews. Furthermore, the Institute of Medicine (IOM) 2009 guidelines were used to obtain the total GWG. RESULTS: PP BMI was used to categorise the 195 pregnant women as overweight/obese (43.1%), normal (46.7%) and underweight (10.2%). There were 53.3%, 34.4% and 12.3% of women who had inadequate, adequate and excessive GWG, respectively. The multinomial logistic regression model indicated that overweight or obese women at the pre-pregnancy stage were 4.09 times more likely to have an excessive rate of GWG (AOR = 4.09, 95% CI: 1.38-12.12, p = 0.011) than those whose weight was normal. Furthermore, women with excessive GWG were 27.11 times more likely to have a baby with macrosomia (AOR = 27.11, 95% CI: 2.99-245.14) (p = 0.001) and those with inadequate GWG were 9.6 times more likely to give birth to a baby with low birth weight (LBW) (AOR = 9.60, 95% CI; 0.88-105.2) (p = 0.002). CONCLUSIONS: This study demonstrates that the malnutrition status prior to pregnancy and inadequate or excessive GWG status during pregnancy as significant risk factors for developing adverse pregnancy outcomes. These findings highlight the importance of providing information, preconception counselling and health education on weight management for healthy pregnancies.

Impact of Genetic Risk Score and Dietary Protein Intake on Vitamin D Status in Young Adults from Brazil.

Given the relationship between vitamin D deficiency (VDD) and adverse outcomes of metabolic diseases, we investigated the interplay of dietary and genetic components on vitamin D levels and metabolic traits in young adults from Brazil. Genetic analysis, dietary intake, and anthropometric and biochemical measurements were performed in 187 healthy young adults (19−24 years). Genetic risk scores (GRS) from six genetic variants associated with vitamin D (vitamin D-GRS) and 10 genetic variants associated with metabolic disease (metabolic-GRS) were constructed. High vitamin D-GRS showed a significant association with low 25(OH)D concentrations (p = 0.001) and high metabolic-GRS showed a significant association with high fasting insulin concentrations (p = 0.045). A significant interaction was found between vitamin D-GRS and total protein intake (g/day) (adjusted for non-animal protein) on 25(OH)D (pinteraction = 0.006), where individuals consuming a high protein diet (≥73 g/d) and carrying >4 risk alleles for VDD had significantly lower 25(OH)D (p = 0.002) compared to individuals carrying ≤4 risk alleles. Even though our study did not support a link between metabolic-GRS and vitamin D status, our study has demonstrated a novel interaction, where participants with high vitamin D-GRS and consuming ≥73 g of protein/day had significantly lower 25(OH)D levels. Further research is necessary to evaluate the role of animal protein consumption on VDD in Brazilians.

GeNuIne (gene-nutrient interactions) Collaboration: towards implementing multi-ethnic population-based nutrigenetic studies of vitamin B12 and D deficiencies and metabolic diseases.

Gene-nutrient interactions (GeNuIne) collaboration, a large-scale collaborative project, has been initiated to investigate the impact of gene-nutrient interactions on cardiometabolic diseases using population-based studies from ethnically diverse populations. In this project, the relationship between deficiencies of vitamins B12 and D, and metabolic diseases was explored using a nutrigenetic approach. A genetic risk score (GRS) analysis was used to examine the combined effect of several genetic variations that have been shown to be associated with metabolic diseases and vitamin B12 and D deficiencies, respectively. In Sri Lankan, Indonesian and Brazilian populations, those carrying a high B12-GRS had an increased risk of metabolic diseases under the influence of dietary protein, fibre and carbohydrate intakes, respectively; however, in Asian Indians, genetically instrumented metabolic disease risk showed a significant association with low vitamin B12 status. With regards to nutrigenetic studies on vitamin D status, although high metabolic-GRS showed an interaction with dietary carbohydrate intake on vitamin D status, the study in Indonesian women demonstrated a vitamin D GRS-carbohydrate interaction on body fat percentage. In summary, these nutrigenetic studies from multiple ethnic groups have provided evidence for the influence of the dietary factors on the relationship between vitamin B12/D deficiency and metabolic outcomes. Furthermore, these studies highlight the existence of genetic heterogeneity in gene-diet interactions across ethnically diverse populations, which further implicates the significance of personalised dietary approaches for the prevention of these micronutrient deficiencies and metabolic diseases.

Interaction between Vitamin D-Related Genetic Risk Score and Carbohydrate Intake on Body Fat Composition: A Study in Southeast Asian Minangkabau Women.

Metabolic diseases have been shown to be associated with low vitamin D status; however, the findings have been inconsistent. Hence, the objective of our study was to investigate the relationship between vitamin D status and metabolic disease-related traits in healthy Southeast Asian women and examine whether this relationship was modified by dietary factors using a nutrigenetic study. The study included 110 Minangkabau women (age: 25-60 years) from Padang, Indonesia. Genetic risk scores (GRS) were constructed based on five vitamin D-related single nucleotide polymorphisms (SNPs) (vitamin D-GRS) and ten metabolic disease-associated SNPs (metabolic-GRS). The metabolic-GRS was significantly associated with lower 25-hydroxyvitamin D (25(OH)D) concentrations (p = 0.009) and higher body mass index (BMI) (p = 0.016). Even though the vitamin D-GRS had no effect on metabolic traits (p > 0.12), an interaction was observed between the vitamin D-GRS and carbohydrate intake (g) on body fat percentage (BFP) (pinteraction = 0.049), where those individuals who consumed a high carbohydrate diet (mean ± SD: 319 g/d ± 46) and carried >2 vitamin D-lowering risk alleles had significantly higher BFP (p = 0.016). In summary, we have replicated the association of metabolic-GRS with higher BMI and lower 25(OH)D concentrations and identified a novel interaction between vitamin D-GRS and carbohydrate intake on body fat composition.

Comment: "Evaluation of the Association of Omentin 1 rs2274907 A>T and rs2274908 G>A Gene Polymorphisms with Coronary Artery Disease in Indian Population: A Case Control Study".

The study by Jha et al. (2019) demonstrated an association of the single nucleotide polymorphism (SNP) rs2274907 A>T with coronary artery disease (CAD) in 100 CAD patients and 100 matched healthy controls from a South Indian population. There are serious concerns with regard to the interpretations of the study findings. The genotypes of the SNP are not in Hardy-Weinberg equilibrium (HWE) in both cases (p < 0.0001) and controls (p = 0.006), which is indicative of a technical error due to a problematic genotyping method. In addition, the genotype and allele frequencies reported in the study do not match with the frequencies listed in the SNP database for Asian Indians. While the study by Jha et al. reported "T" allele as the minor allele, the dbSNP database reported "A" as the minor allele. In summary, it can be concluded that the data presented in the study suffer from genotyping as well as data interpretation error and, hence, the findings should be considered by the reader with caution.

A Nutrigenetic Approach to Investigate the Relationship between Metabolic Traits and Vitamin D Status in an Asian Indian Population.

Studies in Asian Indians have examined the association of metabolic traits with vitamin D status. However, findings have been quite inconsistent. Hence, we aimed to explore the relationship between metabolic traits and 25-hydroxyvitamin D [25(OH)D] concentrations. We investigate whether this relationship was modified by lifestyle factors using a nutrigenetic approach in 545 Asian Indians randomly selected from the Chennai Urban Rural Epidemiology Study (219 normal glucose tolerant individuals, 151 with pre-diabetes and 175 individuals with type 2 diabetes). A metabolic genetic risk score (GRS) was developed using five common metabolic disease-related genetic variants. There was a significant interaction between metabolic GRS and carbohydrate intake (energy%) on 25(OH)D (Pinteraction = 0.047). Individuals consuming a low carbohydrate diet (≤62%) and those having lesser number of metabolic risk alleles (GRS ≤ 1) had significantly higher levels of 25(OH)D (p = 0.033). Conversely, individuals consuming a high carbohydrate diet despite having lesser number of risk alleles did not show a significant increase in 25(OH)D (p = 0.662). In summary, our findings show that individuals carrying a smaller number of metabolic risk alleles are likely to have higher 25(OH)D levels if they consume a low carbohydrate diet. These data support the current dietary carbohydrate recommendations of 50%-60% energy suggesting that reduced metabolic genetic risk increases 25(OH)D.

A nutrigenetics approach to study the impact of genetic and lifestyle factors on cardiometabolic traits in various ethnic groups: findings from the GeNuIne Collaboration.

Several studies on gene-diet interactions (nutrigenetics) have been performed in western populations; however, there are only a few studies to date in lower middle-income countries (LMIC). A large-scale collaborative project called gene-nutrient interactions (GeNuIne) Collaboration, the main objective of which is to investigate the effect of GeNuIne on cardiometabolic traits using population-based studies from various ethnic groups, has been initiated at the University of Reading, UK. While South Asians with higher genetic risk score (GRS) showed a higher risk of obesity in response to a high-carbohydrate diet, South East and Western Asian populations with higher GRS showed an increased risk of central obesity in response to a high-protein diet. The paper also provides a summary of other gene-diet interaction analyses that were performed in LMIC as part of this collaborative project and gives an overview of how these nutrigenetic findings can be translated to personalised and public health approaches for the prevention of cardiometabolic diseases such as obesity, type 2 diabetes and CVD.

Depression increases the genetic susceptibility to high body mass index: Evidence from UK Biobank.

BACKGROUND: This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among individuals with or without depression. METHODS: We used data on 251,125 individuals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)-related genetic risk score (GRSMDD ) as an instrument for depression. We also examined whether depression modifies genetic susceptibility to high BMI, by investigating the interaction between depression and the BMI-related GRSBMI . RESULTS: We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04-0.13). Further, the contribution of genetic risk to high BMI was higher among individuals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD; 95%CI 0.23-0.25) higher BMI among depressed individuals compared to 0.20 SD (95%CI 0.19-0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an individual of average height. Amongst the individual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic-pituitary adrenal axis (pinteraction = 5.7 × 10-5 ). CONCLUSION: Genetic predisposition to high BMI was higher among depressed than to nondepressed individuals. This study provides support for a possible role of MC4R in the link between depression and obesity.

Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population.

BACKGROUND: Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity. METHODS: A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model. RESULTS: The GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed. CONCLUSION: The study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.

BACKGROUND: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. METHODS: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. RESULTS: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. CONCLUSION: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts.

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

BACKGROUND: Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids. METHODS: The DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks. RESULTS: After the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n = 33; -0.71 ± 1.88 mmol/l) compared to the SFA (n = 38; 0.34 ± 0.55 mmol/l) or n-6 PUFA diets (n = 37; -0.08 ± 0.73 mmol/l) (P = 0.004). None of the interactions were statistically significant for the other SNPs. CONCLUSIONS: In summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov as NCT01478958.

Association of the tumor necrosis factor-alpha promoter polymorphism with change in triacylglycerol response to sequential meals.

BACKGROUND: Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant's body weight. Hence, we investigated the association of TNFA polymorphism (-308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia. METHODS: The study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders. RESULTS: The -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts. CONCLUSIONS: Our findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies. TRIAL REGISTRATION: NCT01172951 .

Erratum to: Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population.

[This corrects the article DOI: 10.1186/s12986-016-0098-6.].

Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population.

BACKGROUND: Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity-associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). METHODS: The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. RESULTS: There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the 'A' allele carriers had 2.46 times increased risk of obesity than those with 'CC' genotype (P = 3.0 × 10(-5)) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3(rd) tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with 'T' allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the 'A' allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with 'CC' genotype (P = 4.0 × 10(-5)). CONCLUSIONS: This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.

Impact of Lipoprotein Lipase Gene Polymorphism, S447X, on Postprandial Triacylglycerol and Glucose Response to Sequential Meal Ingestion.

Lipoprotein lipase (LPL) is a key rate-limiting enzyme for the hydrolysis of triacylglycerol (TAG) in chylomicrons and very low-density lipoprotein. Given that postprandial assessment of lipoprotein metabolism may provide a more physiological perspective of disturbances in lipoprotein homeostasis compared to assessment in the fasting state, we have investigated the influence of two commonly studied LPL polymorphisms (rs320, HindIII; rs328, S447X) on postprandial lipaemia, in 261 participants using a standard sequential meal challenge. S447 homozygotes had lower fasting HDL-C (p = 0.015) and a trend for higher fasting TAG (p = 0.057) concentrations relative to the 447X allele carriers. In the postprandial state, there was an association of the S447X polymorphism with postprandial TAG and glucose, where S447 homozygotes had 12% higher TAG area under the curve (AUC) (p = 0.037), 8.4% higher glucose-AUC (p = 0.006) and 22% higher glucose-incremental area under the curve (IAUC) (p = 0.042). A significant gene-gender interaction was observed for fasting TAG (p = 0.004), TAG-AUC (Pinteraction = 0.004) and TAG-IAUC (Pinteraction = 0.016), where associations were only evident in men. In conclusion, our study provides novel findings of an effect of LPL S447X polymorphism on the postprandial glucose and gender-specific impact of the polymorphism on fasting and postprandial TAG concentrations in response to sequential meal challenge in healthy participants.

Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARγ Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study.

BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein ß (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.